This project will characterize to what extent the type and amount of IgG antibody displayed on a platelet surface mediates the immune destruction of platelets in human thrombocytopenia. This will be carried out in three major research efforts. In the first, normal platelets will be sensitized in vitro with antisera from patients with post-transfusion purpura (anti PLA1), platelet transfusion resistance (Anti HLA) and immune thrombocytopenia purpura (ITP) or sensitized in vivo in patients with ITP. The platelets will then be studied in regards to monocyte Fc receptor binding and/or phagocytosis and separate aliquots analyzed for the amount of immune components present on the platelet surface. Quantitation of platelet IgG and IgG subclasses will be carried out using a monoclonal 125I anti-IgG assay. In this way the various types of antisera can be characterized as to their ability to mediate Fc receptor activity and to relate binding and/or ingestion with severity of thrombocytopenia and display of IgG subclasses on the platelet surface. The second thrust of the research project will be to determine whether the presence of autoimmune disease (ITP) alters the ability of effector cell Fc receptors to interact with antibody coated platelets and if this altered Fc receptor activity is reversible in vivo and in vitro. Finally, studies will be carried out to characterize the ability of therapeutic agents found to be useful in ITP to alter monocyte Fc receptor binding and/or phagocytosis of sensitized platelets. These studies will include corticosteroids, vinca alkaloids, colchicine and gamma globulin as therapeutic agents. The studies in patients provide a system to examine treatment modalities which may alter platelet destruction in vivo. These observations may well provide data with prognostic and/or therapeutic implications (e.g., steroid or gamma globulin resistance, etc.). These studies will thus provide new information as regards the pathogenesis and mechanisms operable in antibody mediated destruction of platelets.